The clinical effectiveness of corticoids is related to four basic properties: vasoconstriction, antiproliferative effects, immunosuppression, and anti-inflammatory effects. Topical steroids cause the capillaries in the superficial dermis to constrict, thus reducing erythema. The ability of a given glucocorticoid agent to cause vasoconstriction usually correlates with its anti-inflammatory potency. Vasoconstrictor assays are used in the art and by the U.S. Food and Drug Administration for determining the potency of topical corticosteroid preparations. Topical glucocorticoid preparations have been divided in the field into seven classes based on potency based on double-blind clinical studies and vasoconstrictor assays. Class 1 includes the most potent, while class 7 contains the least potent.
The following glucocorticoid preparations were designated in Fitzpatrick, Dermatology in General Medicine, 5th edition, CD-ROM, 1999, Table 243-1, with the following classes.
TABLE 1CorticosteroidPreparationCorticosteroidClassSourceTemovate ®Clobetasone propionate1Glaxo WellcomeCream 0.05%Temovate ®Clobetasone propionate1Glaxo Wellcomeointment 0.05%Diprolene ®Betamethasone1Schering Corp.cream 0.05%dipropionateDiprolene ®Betamethasone1Schering Corp.ointment 0.05%dipropionatePsorcon ®Diflorasone diacetate1DermikointmentLaboratories, Inc.Cyclocort ®Amcinonide2Fujisawaointment 0.1%Diprolene ®Betamethasone2Schering Corp.cream AFdipropionate0.05%Diprosone ®Betamethasone2Schering Corp.ointment 0.05%dipropionateElocon ®Mometasone furoate2Schering Corp.ointment 0.1%Florone ®Diflorasone diacetate2Dermikointment 0.05%Halog ® creamHalcinonide2Westwood-Squibb0.1%Lidex ® gelFluocinonide2Medicis Pharma-0.05%ceuticals Corp.Lidex ® creamFluocinonide2Medicis Pharma-0.05%ceuticals Corp.Lidex ®Fluocinonide2Medicis Pharma-ointment 0.05%ceuticals Corp.Maxiflor ®Diflorasone diacetate2Allergan Herbertointment 0.05%Topicort ®Desoximetasone2Medicis Pharma-cream 0.25%ceuticals Corp.Topicort ® gelDesoximetasone2Medicis Pharma-0.05%ceuticals Corp.Topicort ®Desoximetasone2Medicis Pharma-ointment 0.25%ceuticals Corp.Aristocort A ®Triamcinolone acetonide3Fujisawaointment 0.1%Cutivate ®Fluticasone propionate3Glaxo Wellcomeointment0.005%Cyclocort ®Amcinonide3Fujisawacream 0.1%Cyclocort ®Amcinonide3FujisawaLotion 0.1%Diprosone ®Betamethasone3Schering Corp.cream 0.05%dipropionateFlorone ® creamDiflorasone diacetate3Dermik0.05%Halog ®Halcinonide3Westwood-Squibbointment 0.1%Lidex ® EFluocinonide3Medicis Pharma-cream 0.05%ceutical Corp.Maxiflor ®Diflorasone diacetate3Allergan Herbertcream 0.05%Valisone ®Betamethasone valerate3Schering Corp.ointment 0.1%Cordran ®Flurandrenolide4Oclassenointment 0.05%Elocon ® creamMometasone furoate4Schering Corp.0.1%Kenalog ®Triamcinolone acetonide4Westwood-Squibbcream 0.1%Synalar ®Fluocinolone acetonide4Medicis Pharma-ointmentceuticals Corp.0.025%Westcort ®Hydrocortisone valerate4Westwood-Squibbointment 0.2%Cordran ®Flurandrenolide5Oclassencream 0.05%Cutivate ®Fluticasone propionate5Glaxo Wellcomecream 0.05%Diprosone ®Betamethasone5Schering Corp.lotion 0.05%dipropionateKenalog ®Triamcinolone acetonide5Westwood-Squibblotion 0.1%Locoid ® creamHydrocortisone butyrate5Ferndale0.1%Synalar ® creamFlucinolone acetonide5Medicis Pharma-0.025%ceuticals Corp.Valisone ®Betamethasone valerate5Schering Corp.cream 0.1%Westcort ®Hydrocortisone valerate5Westwood-Squibbcream 0.2%Aclovate ®Alclometasone6Glaxo Wellcomecream 0.05%dipropionateAclovate ®Alclometasone6Glaxo Wellcomeointment 0.05%dipropionateAristocort ®Triamcinolone acetonide6Fujisawacream 0.1%Desowen ®Desonide6Galdermacream 0.05%Synalar ®Fluocinolone acetonide6Medicis Pharma-solution 0.01%ceuticals Corp.Synalar ®Fluocinolone acetonide6Medicis Pharma-cream 0.01%ceuticals Corp.Tridesilon ®Desonide6Milescream 0.05%Valisone ®Betamethasone valerate6Schering Corp.lotion 0.1%Topicals with7hydrocortisonedexamethasone,flumethasone,prednisolone,andmethylprednisoloneAll percentages given are weight percentages unless otherwise noted.
Although there is no significant difference between potencies within Class 2, within Class 1 Temovate® cream or ointment is significantly more potent than Class 1 Diprolone® cream or ointment of Schering and Class 1 Psorcon® ointment of Dermik Laboratories, Inc.
Several factors such as the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings affect the percutaneous absorption and resulting potency of corticosteroids regardless of the intrinsic potency of the glucocorticosteroid (or glucocorticoid) molecule. Further, inflammation and/or other disease processes in the skin increase percutaneous absorption.
The vehicle in which the corticoid is incorporated may be as important as the corticoid molecule itself in determining the potency of a given formulation because the vehicle affects the amount of corticoid that is released in any given period of time, and its absorption. In many corticosteroid compositions, the vehicle is as much as 99% of the total composition. Very occlusive vehicles, such as ointments (water-insoluble mixtures of oil and petrolatum), increase the corticosteroid effect because they provide increased hydration of the stratum corneum and increase the skin's permeability. By covering the skin with an occlusive dressing such as plastic wrap, this effect can be heightened as much as 100-fold. The solubility of the corticoid in the vehicle also affects penetration into the skin.
Creams, which are suspensions of oil in water, have also been used as vehicles for corticosteroids. The compositions of creams vary and are far less greasy than ointments but do not provide the same degree of hydration to the skin, and therefore may not have as high penetration as ointments. Lotions, which are suspensions of oil in water and are similar to creams, are vehicles which include agents to help solubilize the corticosteroids. Solutions have been used as vehicles and are water based with propylene glycol. Gels are solid components at room temperature but melt on the skin. Lotions, gels and solutions have less penetration than ointments.
Many vehicles for corticosteroids include propylene glycol for dissolving the corticosteroid in the vehicle. In general, compositions that contain higher amounts of propylene glycol tend to be more potent.
Vehicles are so important in the potency of corticosteroids that different formulations containing the same amount of the same corticosteroid often are in different potency classes. For example, commercially available preparations of 0.05% betamethasone dipropionate are classified as having Class 1, Class 2 or Class 3 potency, depending on their vehicles (as seen in Table 1).